Childhood-onset systemic lupus erythematosus with trisomy X and the increased risk for bone complications: a case report.

BACKGROUND: Systemic lupus erythematosus is a multi-organ inflammatory autoimmune disease; immune complexes are part of the pathogenesis, but not entirely responsible. Trisomy X is the most common female chromosomal abnormality and the role of an additional X chromosome in the development of systemic lupus erythematosus is well recognized. However, the potential complications and optimal management of childhood lupus with trisomy X remain unclear. Herein, we describe a case of childhood-onset systemic lupus erythematosus associated with severe bone complications presumably secondary to trisomy X. CASE PRESENTATION: A 16-year-old Japanese girl was diagnosed with childhood-onset systemic lupus erythematosus and trisomy X. A chromosomal abnormality (47, XXX) was incidentally identified on bone marrow examination initially done to determine the cause of pancytopenia. She had a persistent headache, fever　for six days, diffuse hair loss, mucosal ulcers, butterfly eruptions, and palmar erythema. Furthermore, thrombocytopenia, anemia, and erythrocyte fragmentation were detected, suggesting secondary thrombotic microangiopathy. She was initially treated with intravenous methylprednisolone pulse therapy and prescribed monthly cyclophosphamide for severe disease activity, prednisolone, mycophenolate mofetil, and hydroxychloroquine as remission maintenance drugs. She developed generalized extremity pain that had been worsening throughout the disease. Extremity magnetic resonance imaging performed 12 months after the treatment onset revealed multifocal avascular necrosis, and dual-energy X-ray absorptiometry revealed further decreased bone mineral density. High plasma levels of factor VIII were detected by additional tests for coagulation functions, and we suspected the possibility that factor VIII might cause avascular necrosis due to thrombosis. Currently, she is being treated with prednisolone and MMF for SLE. However, her extremity pain has not been managed effectively even under the administration of non-steroidal anti-inflammatory drugs and pregabalin. CONCLUSIONS: An additional X chromosome has been reported to be associated with factor VIII and osteoporosis. Additionally, elevated plasma levels of FVIII is the risk factors for thrombosis, which leads to the risk of avascular necrosis. Patients with systemic lupus erythematosus complicated by trisomy X might be at a higher risk of avascular necrosis and osteoporosis that can also manifest in childhood systemic lupus erythematosus.

Evaluation of SPECT/CT in the assessment of inflammatory jaw pathologies.

PURPOSE: Since accurate diagnosis of inflammatory jaw diseases is still challenging, this study investigated the performance of three phase bone scintigraphy including SPECT/CT in the assessment of correct diagnosis and size of the affected bone tissue. METHOD: This retrospective study contained 31 patients with suspected jaw-related osteoradionecrosis, osteomyelitis or medication-related osteonecrosis of the jaw, which underwent 3-phase bone scintigraphy including SPECT/CT. Results were reviewed by two nuclear medicine physicians. Positive cases received surgery; negative ones were followed-up for six months. Both served as reference standard. Inflamed bone length was measured in the SPECT/CT images and postoperatively by a pathologist. RESULTS: 19 out of 20 positive cases and 10 out of 11 negative ones were classified correctly by SPECT/CT (sensitivity 95 %, specificity 91 %, accuracy 94 %, positive predictive value 95 %, negative predictive value 91 %). Regarding the length of affected bone, no significant difference (p = 0.23) could be observed between SPECT/CT and postoperative obtained values. Both correlated significantly (r = 0.86, p = 0.0001). CONCLUSION: SPECT/CT can safely detect different kinds of inflammatory jaw pathologies compared to other conventional imaging modalities. Lack of specificity of conventional scintigraphy ranging from 17 % to 71 % in earlier studies could be improved by adding CT-analysis. Additionally, SPECT/CT assists the surgeon in determining the expansion of the process (with focus on the length) preoperatively and thereby optimizing surgery planning.

Pathology Assessment of Femoral Head Resection Specimens: An Important Quality Assurance Procedure.

CONTEXT.­: Decisions to perform hip arthroplasty rely on both radiographic and clinical findings. Radiologists estimate degree of osteoarthritis (OA) and document other findings. Arthroplasty specimens are sometimes evaluated by pathology. OBJECTIVE.­: To determine the frequency of pathologic changes not recognized clinically. DESIGN.­: Nine hundred fifty-three consecutive femoral head resections performed between January 2015 and June 2018, with recent radiologic and histologic study, were reviewed. We compared severity of OA reported by radiology and pathology. Findings unrecognized radiographically but recorded pathologically, and discrepancies between clinical diagnosis and pathology diagnosis, were tabulated. RESULTS.­: Twenty-one cases of osteomyelitis were diagnosed radiographically or pathologically. Eight discrepancies were present. Fourteen osteomyelitis cases were recognized clinically. Pathology recognized 2 neoplasms missed radiographically. Avascular necrosis was diagnosed on pathology but not radiology in 25 cases, and 35 cases of avascular necrosis were seen radiographically but not pathologically. Osteoarthritis was graded both radiographically and pathologically from 0 to 3. Five hundred ninety-one of 953 cases (62%) were grade 3. Pathologists and radiologists had perfect agreement in 696 of 953 cases (73%). When grade of OA seen at pathology was correlated with surgeon, 2 groups of surgeons were detected: one with a low threshold for performance of hip arthroplasty (23%-28% low-severity OA) and the second with a high threshold (2%-5% low-severity OA). CONCLUSIONS.­: Correlation between radiology and pathology diagnoses is high. Degree of OA present varies significantly between surgeons. Pathology discloses findings not recognized clinically.

Is there a trend in CT scanning scaphoid nonunions for deformity assessment?-A systematic review.

PURPOSE: The effect of scaphoid nonunion deformity on wrist function is uncertain due to the lack of reliable imaging tools. Advanced three-dimensional (3-D) computed tomography (CT)-based imaging techniques may improve deformity assessment by using a mirrored image of the contralateral intact wrist as anatomic reference. The implementation of such techniques depends on the extent to which conventional CT is currently used in standard practice. The purpose of this systematic review of medical literature was to analyze the trend in CT scanning scaphoid nonunions, either unilaterally or bilaterally. MATERIALS AND METHODS: Using Medline and Embase databases, two independent reviewers searched for original full-length clinical articles describing series with at least five patients focusing on reconstructive surgery of scaphoid nonunions with bone grafting and/or fixation, from the years 2000-2015. We excluded reports focusing on only nonunions suspected for avascular necrosis and/or treated with vascularized bone grafting, as their workup often includes magnetic resonance imaging. For data analysis, we evaluated the use of CT scans and distinguished between uni- and bilateral, and pre- and postoperative scans. RESULTS: Seventy-seven articles were included of which 16 were published between 2000 and 2005, 19 between 2006 and 2010, and 42 between 2011 and 2015. For these consecutive intervals, the rates of articles describing the use of pre- and postoperative CT scans increased from 13%, to 16%, to 31%, and from 25%, to 32%, to 52%, respectively. Hereof, only two (3%) articles described the use of bilateral CT scans. CONCLUSION: There is an evident trend in performing unilateral CT scans before and after reconstructive surgery of a scaphoid nonunion. To improve assessment of scaphoid nonunion deformity using 3-D CT-based imaging techniques, we recommend scanning the contralateral wrist as well.

Development of an imaging mitigation strategy for patient enrolment in the tanezumab nerve growth factor inhibitor (NGF-ab) program with a focus on eligibility assessment.

OBJECTIVE: Nerve growth factor antibodies (NGF-ab) have shown promising analgesic efficacy. Aim was to describe reader training efforts and present reliability data focusing on radiographic eligibility in the tanezumab program. METHODS: A multi-step process was used for reader calibration and reliability testing. First, a reference standard set of cases was created and diagnostic performance was evaluated. A second exercise focused on agreement of ordinal assessment (Kellgren-Lawrence grading) of radiographic osteoarthritis. Subsequently, 11 readers were trained and read a test set of 100 cases focused on eligibility assessments. Additional reliability testing and calibration of five core readers assessing eligibility of 30 cases was performed 3 and 6 months after study start. RESULTS: Sensitivity for the reference standard readings ranged from 0.50 to 0.90 and specificity from 0.40 to 0.83. Overall agreement for Kellgren-Lawrence grading ranged from 71.4% to 82.9%. For the 11 reader exercise, in 76% of cases at least 8 of 11 readers agreed on eligibility status. For the reliability testing 3 months after study start, in 80.0% of cases at least 4 of 5 readers agreed on eligibility with a κ = 0.43 (95% CI: 0.32-0.54). For the reliability testing after 6 months, in 83.3% of cases at least 4 of 5 readers agreed on eligibility with a κ = 0.52 (95% CI: 0.41-0.63). CONCLUSIONS: After intense efforts spent in the development of an imaging program for an NGF-ab clinical program, the achieved reliability for eligibility assessment is substantial but not perfect. Ongoing efforts of calibration prior to including additional readers to the program and during study conduct between current readers will be needed to ensure agreement on potential adverse events and radiographic disease severity.

Beta-tricalcium phosphate for orthopedic reconstructions as an alternative to autogenous bone graft.

Autogenous bone graft (autograft) remains the gold standard in the treatment of many orthopedic problems. However, graft harvest can lead to perioperative morbidity and increased cost. We tested the hypothesis that an osteoconductive matrix, beta-tricalcium phosphate (ß-TCP), would be a safe and effective alternative to autograft alone. Beta-tricalcium phosphate (ß-TCP) is considered as one of the most promising biomaterials for bone reconstruction. This study analyzes the outcomes of patients who received ß-TCP as bone substitutes in orthopedic surgery. METHODS: A total of 50 patients were enrolled in a controlled, non-inferiority clinical trial to compare the safety and efficacy of ß-TCP (25 patients) with those of autograft (25 patients) in indications requiring usually autograft. These 50 patients were categorized according to the etiology and morphology of the 54 bone defects resulting from elective surgical procedures, such as 34 open-wedge high tibial osteotomies, and 20 osteonecrosis treatments with core decompression. Radiographic (healing process with or without integration of ß-TCP), clinical (no other surgical procedure), functional outcomes and safety (with or without complications) were assessed through fifty-two weeks postoperatively. RESULTS: With regard to the primary endpoint (radiographic evolution), the fusion rate of the 34 open-wedge osteotomies was 100% (17 among 17) for patients in the group with ß-TCP compared with 94% (16 among 17) for patients in the autograft group. For the 20 cavitary defects (osteonecrosis), the radiographic union rates, as determined by the presence of osseous bridging, were 100% for patients in the group with ß-TCP and 100% for those in the autograft group. Clinically at one year, all quality-of-life and functional outcome data supported non-inferiority of ß-TCP compared with autograft, and patients in the ß-TCP group were found to have less pain and an improved safety profile. CONCLUSIONS: Treatment with ß-TCP resulted in comparable fusion rates, less pain and fewer side effects as compared with treatment with autograft. This study established clinical parameters where the ß-TCP alone can successfully support the osteogenic process.

Ultrasound imaging for the rheumatologist. XLII. Assessment of hip pain in rheumatic patients: the radiologist's view.

Hip pain is a common complaint in daily practice and the identification of the underlying pathologic condition is the first step for an adequate treatment. In this review, we discuss the available evidence for the application of conventional radiography, computed tomography and magnetic resonance imaging in rheumatologic patients with painful hip, presenting the main imaging findings due to osteoarthritis, inflammatory arthritis (rheumatoid arthritis and spondyloarthritides), osteonecrosis and some other soft tissue involvement (bursitis and synovial cyst) that could be the cause of hip pain. Because different imaging techniques show different sensitivity and specificity, the choice of technique to use depends on the type and stage of the disease itself.

Freiberg's disease: quantitative assessment of osteonecrosis on three-dimensional CT.

BACKGROUND: The extent of necrosis is the main determining factor in the outcome of osteonecrosis. There is no method for measuring the extent of osteonecrosis of the metatarsal head in Freiberg's disease. The purpose of this study was to determine the reliability and prognostic ability of a new method for measurement of the extent of osteonecrosis in Freiberg's disease on three-dimensional computed tomography. METHODS: A retrospective review of 11 cases with symptomatic Freiberg's disease in ten patients (5 males and 5 females; mean age, 27 years) undergoing computed tomography between July 2005 and September 2007 was performed. Two investigators (K.A.C. and H.K.O.) used a new method to measure the necrotic extent of the metatarsal head: the necrotic angle ratio of necrotic arc angle to normal arc angle of the articular surface on the sagittal reconstruction image of computed tomography. The interobserver reliability was determined for computed tomography measurement. Correlation between the Smillie staging using radiographs and the necrotic angle ratio on computed tomography was also evaluated. RESULTS: One patient presented with stage I disease (Smillie staging), one with stage II, two with stage III, five with stage IV, and two with stage V, respectively. The necrotic angle ratio of the metatarsal head was 14% in stage I, 21% in stage II, 34% in stage III, 43% in stage IV, and 53% in stage V. The interobserver reliability for computed tomography measurement was high (Cronbach α=0.96). We found the increase of the necrotic extent in proportion to the Smillie stage. The Smillie staging using radiographs and the necrotic angle ratio on computed tomography were significantly correlated. (P<0.05) CONCLUSIONS: Three-dimensional computed tomography measurement of the necrotic extent of the metatarsal head is a reliable and useful method in evaluating the staging of Freiberg's disease and may eventually help to optimize treatment.

Kohler disease: diagnoses and assessment by bone scintigraphy.

Limping is a frequent occurrence in children and may be caused by various conditions, including trauma, inflammation, infection, and malignancy. Nontraumatic avascular necrosis of the tarsal bones should be included in the differential diagnosis. Accumulated data have supported the superiority of bone scans to radiography in the early diagnosis of avascular necrosis. Bone scintigraphy is a useful tool for investigating pain when symptoms, laboratory examinations, and radiography do not point to a specific diagnosis. In the early phase of disease, bone scans may demonstrate decreased tracer uptake (photopenic region), subsequently a hot area is seen during the reparative process. Although magnetic resonance imaging has important implications in the diagnosis of avascular necrosis, bone scintigraphy with its ready availability has a significant role as a primary tool in the evaluation of a limping child.

Incidence, risk factors and management of osteonecrosis of the jaw in patients with multiple myeloma: a single-centre experience in 303 patients.

The incidence, characteristics and risk factors for the development of osteonecrosis of the jaw (ONJ) were evaluated among 303 myeloma patients. Only patients who received bisphosphonates developed ONJ (28/254; 11%). Zoledronic acid produced 9.5-fold greater risk for developing ONJ than pamidronate alone (P = 0.042) and 4.5-fold greater risk than subsequent use of pamidronate + zoledronic acid (P = 0.018). Use of thalidomide and number of bisphosphonate infusions also increased the risk for ONJ by 2.4-fold (P = 0.043), and 4.9-fold respectively (P = 0.012). ONJ developed earlier among patients receiving zoledronic acid. Our data indicates that administration of zoledronic acid for more than 2 years or in combination with thalidomide requires caution in myeloma.

The Lichtman classification for Kienböck's disease: an assessment of reliability.

PURPOSE: The correct identification of Lichtman stage 3A and 3B Kienböck's disease is crucial for treatment purposes. The present study evaluates the reliability of the Lichtman classification, with specific attention to differentiating stage 3A and 3B. METHODS: Four reviewers evaluated wrist radiographs from 39 patients with Kienböck's disease. Radiographs were graded according to the traditional Lichtman classification, a modification of the Lichtman classification using a radioscaphoid angle of 60 degrees to subdivide stage 3, and 8 other radiographic measures. RESULTS: The interobserver reliability of the Lichtman classification was substantial (kappa coefficient 0.63), but Stage 3A was less reliably identified (kappa 0.38). The new modification of the Lichtman classification increased both the overall (kappa 0.81) and the stage 3A (kappa 0.75) interobserver reliability. CONCLUSION: The use of the radioscaphoid angle increases the interobserver reliability of the Lichtman classification. This should allow a better understanding of the clinically important distinction between stage 3A and 3B disease.

Bone scanning in the assessment of patellar viability following knee replacement.

In an attempt to diagnose avascular necrosis (AVN) of the patella, a potential complication of the surgical procedure, 99mTc-MDP bone scanning was performed pre- and postoperation in 37 patients treated by 41 total knee arthroplasties. The normal immediate postoperative scan should demonstrate increased radionuclide uptake in the patella when compared to preoperative scans. Decreased uptake was seen in four cases in the early postoperative period. This latter group was believed to be at risk for osteonecrosis and stress fracture of the patella. For this reason, prophylactic restriction of activity was instituted, with subsequent return of normal radionuclide uptake in the patella. Bone scanning provides an effective method of early diagnosis of patients at risk for the development of AVN and secondary patellar fractures following total knee arthroplasty.

The role of bone scans in the assessment of prognosis of scaphoid fractures.

Fifty patients with radiographic evidence of an acute scaphoid fracture were studied prospectively. Technetium bone scans were performed on all patients soon after injury in an attempt to detect fractures at risk of non-union or avascular necrosis. In three patients the scan showed a focal area of decreased radionuclide concentration in the region of the proximal pole of scaphoid implying avascularity, and each developed the radiographic signs of avascular necrosis. Two of these patients, each with a displaced fracture, developed non-union. Acute fractures of the scaphoid with evidence of avascularity on bone scan are at high risk of developing non-union.